The pharmacokinetics and bioavailability, that is the rate of absorption and systemic availability, of a single oral dose of Norpace R (disopyramide Phosphate) relative to an intravenous tracer dose of 14C labelled disopyramide administered simultaneously will be compared in 5 normal subjects and 20 patients with varying degrees of congestive heart failure. The patients will be divided into 4 functional groups consisting of 5 patients per group according to the New York Heart Association functional classifications. Ventricular function will also be assessed by multiple radionuclide cineangiography, systolic time intervals, and treadmill excercise testing. The role of concentration-dependent protein binding in disopyramide pharmacokinetics and bioavailability will be assessed. The extent of hepatic first-pass metabolism will be compared in normal subjects and in patients. The free fraction, f, of total concentrations of disopyramide will be determined by dialyzing the sera of each individual subject against an equal volume of phosphate buffer containing various known concentrations of the drugs. The protein binding of diso-pyramide will be compared in normal subjects and in patients. Total serum and urinary concentrations of disopyramide and its mono-N-dealkylated metabolite will be measured by a specific high-performance liquid chromatographic method developed by the author. Previous studies of the pharmacokinetics and bioavailability of disopyramide have failed to address the drug's pharmacokinetic dependence on concentration, or have failed to appropriately determine the protein binding of the drug in individual subjects. Because of this, erroneous conclusions regarding the pharmacokinetics and bioavailability have been made. The results of the proposed study will lead to more appropriate guidelines for dosing disopyramide in patients, and to a better understanding of how variable protein binding may influence the pharmacokinetics and bioavailability of drugs.